In view of the vital biological activities of the polyhydroxylated trans-stilbenes, here have been a few methods reported for the synthesis of these compounds.
U.S. Pat. No. 6,048,903 describes the synthesis of E-resveratrol by the Wittig reaction of 3,5-dimethoxybenzyltriphenyl phosphonium salt with p-anisaldehyde in the presence of n-butyl lithium. In this method the mixture of Z- and E-olefins so obtained is demethylated with large amount of boron tribromide to get very low yield of the product. This method suffers from the low quality and use of expensive and hazardous reagents.
WO 00/21368 describes the condensation of phosphonate esters with aromatic aldehydes followed by demethylation using pyridine hydrochloride. In this method also the yields are low & the process is not commercially attractive.
Drewes, S. E.; Fletcher, I. P J. Chem. Soc. Perkin Trans. 1 1974, 961-962 & Bajaj, R.; Gill, M. T.; McLaughiln, J. L. Rev. Latinoamer Quim. 1987, 18, 79-80 reported the synthesis of analogs of E-resveratrol wherein a mixture of E- & Z-isomer is obtained.
Cunningham, J.; Haslam, E.; Haworth, R. D. J. Chem. Soc. 1963, 2875-2883 disclosed a different route, which comprises reaction of 3,5-dihydroxyphenylacetate and 3,4-dihydroxybenzaldehyde in acetic anhydride, decarboxylation of the ensuing 3,3′,4,5′-tetraacetoxystilbene-α-carboxylic acid with copper and quinoline at high temperature, and hydrolysis of the resulting piceatannol tetraacetate with sodium hydroxide. The reported yields in these methods are moderate to low.
Ali, M. A.; Kondo, K.; Tsuda, Y. Chem. Pharm. Bull. 1992, 40(5) 1130-1136 described the Wittig reaction, wherein the undesired Z-isomers are reported to form to the extent of 52% along with the desired E-isomers (48%) when potassium tert-butoxide is employed.
Cushman, M.; Nagarathnam, D.; Gopal, D. et al. J. Med. Chem. 1992, 35 (12), 2293-2306; Chen, Yi-Ping; Lei, Tong-Kang. Zhongguo Yiyao Gongye Zazhi 2000, 31(7), 334-336 disclosed the formation of Z-isomers to the extent of 45% (E: 55%) when sodium hydride is used.
All of the above prior art disclosures have following limitations because of which the process is commercially not suitable and hazardous:
A mixture of Z- and E-isomers is always encountered and the isomers are separated by column chromatography or by crystallization techniques. Conversion of Z- into E-isomers with the aid of photochemical techniques are reported, wherein the mixture of Z- and E-isomers are irradiated with high powered lamps in the presence of catalysts like diaryl disulfides at high temperature.
In addition, the disulfides, which are essential for photochemical conversions, produce very bad smell and not environmentally acceptable.
Thus these techniques make the process not preferable for the industrial scale and, more over, these are non eco-friendly.